Adipose tissue engineering based on the controlled release of fibroblast growth factor-2 in a collagen matrix

Adipose tissue forms when basement membrane extract ( Matrigel (TM)) and fibroblast growth factor-2 (FGF-2) are added to our mouse tissue engineering chamber model. A mouse tumor extract, Matrigel is unsuitable for human clinical application, and finding an alternative to Matrigel is essential. In this study we generated adipose tissue in the chamber model without using Matrigel by controlled release of FGF-2 in a type I collagen matrix. FGF-2 was impregnated into biodegradable gelatin microspheres for its slow release. The chambers were filled with these microspheres suspended in 60 mu L collagen gel. Injection of collagen containing free FGF-2 or collagen containing gelatin microspheres with buffer alone served as controls. When chambers were harvested 6 weeks after implantation, the volume and weight of the tissue obtained were higher in the group that received collagen and FGF-2 impregnated microspheres than in controls. Histologic analysis of tissue constructs showed the formation of de novo adipose tissue accompanied by angiogenesis. In contrast, control groups did not show extensive adipose tissue formation. In conclusion, this study has shown that de novo formation of adipose tissue can be achieved through controlled release of FGF-2 in collagen type I in the absence of Matrigel.

Post-translational modification accounts for the presence of varied forms of nerve growth factor in Australian elapid snake venoms

The Australian elapid snakes are amongst the most venomous snakes in the world, but much less is known about the overall venom composition in comparison to Asian and American snakes. We have used a combined approach of cDNA cloning and 2-DE with MS to identify nerve growth factor (NGF) in venoms of the Australian elapid snakes and demonstrate its neurite outgrowth activity While a single 730 nucleotide ORF, coding for a 243 amino acid precursor protein was detected in all snakes, use of 2-DE identified NGF proteins with considerable variation in molecular size within and between the different snakes. The variation in size can be explained at least in part by Winked glycosylation. it is possible that these modifications alter the stability, is necessary to activity and other characteristics of the snake NGFs. Further characterisation delineate the function of the individual NGF isoforms.

A ASCENSÃO CELESTIAL DE PAULO DE TARSO: ANÁLISE DE 2 CORÍNTIOS 12,1-10 A PARTIR DA HISTÓRIA DA RELIGIÃO E DA NEUROTEOLOGIA

O tema viagem celestial , bem familiar ao mundo mediterrâneo antigo fundamenta-se na crença de que o visionário pode cruzar a fronteira entre a humanidade e a divindade, uma característica constante na literatura apocalíptica. O misticismo judaico antigo era visto como uma importante dimensão dessa tradição, razão pela qual os místicos usaram o termo apocalipse para descrever a revelação de suas experiências. A ascensão de Paulo ao céu, recontada em 2 Cor 12,1-10, é o único relato de primeira mão e a melhor evidência para a prática extática de viagem celestial no judaísmo do primeiro século. De grande interesse nos estudos do Novo Testamento o texto tem sido abordado em forma temática que se estende desde o reconhecimento do apóstolo como agradável à divindade o que lhe rendeu tal feito heróico a uma experiência de punição pelos guardiões dos portões celestiais por não ter sido encontrado nele mérito para aproximar-se do lugar da presença de Deus. Por muito tempo os estudos que predominavam na academia eram os de aspectos teológicos da passagem, tais como o espinho na carne , a missão apostólica , os oponentes de Paulo , entre outros. A linguagem da passagem revela pontos importantes não considerados de forma conjunta para uma interpretação coerente do texto. O uso por parte do apóstolo de expressões do círculo místico-apocalíptico judaico, tais como foi arrebatado , Terceiro Céu , ouviu palavras inefáveis e um espinho na carne precisa ser investigado para a compreensão do que Paulo tinha em mente ao utilizar tais terminologias. Outro problema é a omissão do enfoque experimental descrito na passagem. O apóstolo revela que vivenciou tal experiência recontada em 2 Cor 12,1-10. Ao relatar o desconhecimento do status do seu corpo durante a ascensão ele evidencia sinais do estado alterado de consciência, aspecto não considerado nas análises tradicionais do texto. Esses problemas que são abordados nesta tese tomam como instrumentos da análise a História da Religião e o da Neuroteologia. Modelos foram construídos tentando demonstrar uma correlação entre a atividade cerebral e a experiência mística. Há que se destacar, nesse sentido, que o surgimento da neuroteologia ou neurologia espiritual constitui-se em um avanço na área da experiência religiosa. Pontos de difícil interpretação no texto paulino foram elucidados dentro dessa perspectiva. A proposta deste trabalho, portanto, foi construir um quadro contextual em que a experiência extática de Paulo pudesse ser analisada. O estudo possibilitou inferir que a abordagem interdisciplinar permite alcançar um cenário mais apropriado para a compreensão e interpretação do referido texto.

Retail restructuring and consumer choice 2:understanding consumer choice at the household level

This paper complements the preceding one by Clarke et al, which looked at the long-term impact of retail restructuring on consumer choice at the local level. Whereas the previous paper was based on quantitative evidence from survey research, this paper draws on the qualitative phases of the same three-year study, and in it we aim to understand how the changing forms of retail provision are experienced at the neighbourhood and household level. The empirical material is drawn from focus groups, accompanied shopping trips, diaries, interviews, and kitchen visits with eight households in two contrasting neighbourhoods in the Portsmouth area. The data demonstrate that consumer choice involves judgments of taste, quality, and value as well as more ‘objective’ questions of convenience, price, and accessibility. These judgments are related to households’ differential levels of cultural capital and involve ethical and moral considerations as well as more mundane considerations of practical utility. Our evidence suggests that many of the terms that are conventionally advanced as explanations of consumer choice (such as ‘convenience’, ‘value’, and ‘habit’) have very different meanings according to different household circumstances. To understand these meanings requires us to relate consumers’ at-store behaviour to the domestic context in which their consumption choices are embedded. Bringing theories of practice to bear on the nature of consumer choice, our research demonstrates that consumer choice between stores can be understood in terms of accessibility and convenience, whereas choice within stores involves notions of value, price, and quality. We also demonstrate that choice between and within stores is strongly mediated by consumers’ household contexts, reflecting the extent to which shopping practices are embedded within consumers’ domestic routines and complex everyday lives. The paper concludes with a summary of the overall findings of the project, and with a discussion of the practical and theoretical implications of the study.

Mechanism of attenuation of skeletal muscle atrophy by zinc-α2-glycoprotein

The mechanism by which the adipokine zinc-a2-glycoprotein (ZAG) increases the mass of gastrocnemius, but not soleus muscle of diabetic mice, has been evaluated both in vivo and in vitro. There was an increased phosphorylation of both double-stranded RNA-dependent protein kinase and its substrate, eukaryotic initiation factor-2a, which was attenuated by about two-thirds in gastrocnemius but not soleus muscle of ob/ob mice treated with ZAG (50 µg, iv daily) for 5 d. ZAG also reduced the expression of the phospho forms of p38MAPK and phospholipase A2, as well as expression of the ubiquitin ligases (E3) muscle atrophy F-box/atrogin-1 and muscle RING finger protein, and the increased activity of both caspase-3 and casapse-8 to values found in nonobese controls. ZAG also increased the levels of phospho serine-threonine kinase and mammalian target of rapamycin in gastrocnemius muscle and reduced the phosphorylation of insulin receptor substrate-1 (Ser307) associated with insulin resistance. Similar changes were seen with ZAG when murine myotubes were incubated with high glucose concentrations (10 and 25 mm), showing that the effect of ZAG was direct. ZAG produced an increase in cAMP in murine myotubes, and the effects of ZAG on protein synthesis and degradation in vitro could be replicated by dibutyryl cAMP. ZAG increased cAMP levels of gastrocnemius but not soleus muscle. These results suggest that protein accretion in skeletal muscle in response to ZAG may be due to changes in intracellular cAMP and also that ZAG may have a therapeutic application in the treatment of muscle wasting conditions.

Pathological changes in the sporadic and variant forms Of Creutzfeldt-Jakob Disease (CJD) are spatially related to blood vessels

The objective of this article was to determine whether the pathological changes of Creutzfeldt-Jacob disease (CJD) were related to the brain microcirculation. Hence, the spatial correlations between the vacuolation, prion protein (PrP) deposits, and the blood vessel profiles were studied in immunolabelled sections of the cerebral cortex, hippocampus, and cerebellum in two subtypes of CJD, viz., sporadic CJD (sCJD) and variant CJD (vCJD). In sCJD, both the vacuolation and the ‘synaptic-type’ PrP deposits were spatially correlated with the microvessels; the PrP deposits being more strongly correlated than the vacuoles. In vCJD, there were no significant spatial correlations between either the vacuolation or the diffuse-type of PrP deposit and the microvessels. By contrast, a consistent pattern of spatial correlation was observed in gyri of the cerebral cortex between the florid PrP deposits and microvessels. In both sCJD and vCJD, the frequency of positive spatial correlations was similar in the different gyri of the cerebral cortex and in the upper compared with the lower laminae. In conclusion, the microcirculation may be more significantly involved in determining the pathological changes in sCJD than in vCJD. The spatial correlations of the florid PrP deposits in vCJD and the synaptic deposits in sCJD and the blood vessels may be attributable to factors associated with the microcirculation which enhance the aggregation of PrP molecules rather than representing a possible haematogenous spread of the disease. S

Rules for mapping a conceptual model onto various data base management systems. Available in 2 volumes.

The design and implementation of data bases involve, firstly, the formulation of a conceptual data model by systematic analysis of the structure and information requirements of the organisation for which the system is being designed; secondly, the logical mapping of this conceptual model onto the data structure of the target data base management system (DBMS); and thirdly, the physical mapping of this structured model into storage structures of the target DBMS. The accuracy of both the logical and physical mapping determine the performance of the resulting systems. This thesis describes research which develops software tools to facilitate the implementation of data bases. A conceptual model describing the information structure of a hospital is derived using the Entity-Relationship (E-R) approach and this model forms the basis for mapping onto the logical model. Rules are derived for automatically mapping the conceptual model onto relational and CODASYL types of data structures. Further algorithms are developed for partly automating the implementation of these models onto INGRES, MIMER and VAX-11 DBMS.

Education and self-management for people newly diagnosed with type 2 diabetes: a qualitative study of patients' views.

OObjectives: We explored the perceptions, views and experiences of diabetes education in people with type 2 diabetes who were participating in a UK randomized controlled trial of methods of education. The intervention arm of the trial was based on DESMOND, a structured programme of group education sessions aimed at enabling self-management of diabetes, while the standard arm was usual care from general practices. Methods: Individual semi-structured interviews were conducted with 36 adult patients, of whom 19 had attended DESMOND education sessions and 17 had been randomized to receive usual care. Data analysis was based on the constant comparative method. Results: Four principal orientations towards diabetes and its management were identified: `resisters', `identity resisters, consequence accepters', `identity accepters, consequence resisters' and `accepters'. Participants offered varying accounts of the degree of personal responsibility that needed to be assumed in response to the diagnosis. Preferences for different styles of education were also expressed, with many reporting that they enjoyed and benefited from group education, although some reported ambivalence or disappointment with their experiences of education. It was difficult to identify striking thematic differences between accounts of people on different arms of the trial, although there was some very tentative evidence that those who attended DESMOND were more accepting of a changed identity and its implications for their management of diabetes. Discussion: No one single approach to education is likely to suit all people newly diagnosed with diabetes, although structured group education may suit many. This paper identifies varying orientations and preferences of people with diabetes towards forms of both education and self-management, which should be taken into account when planning approaches to education.

The SEC’s retail investor 2.0: Interactive data and the rise of calculative accountability

The Securities and Exchange Commission (SEC) in the United States mandated a new digital reporting system for US companies in late 2008. The new generation of information provision has been dubbed by Chairman Cox, ‘interactive data’ (SEC, 2006a). Despite the promise of its name, we find that in the development of the project retail investors are invoked as calculative actors rather than engaged in dialogue. Similarly, the potential for the underlying technology to be applied in ways to encourage new forms of accountability appears to be forfeited in the interests of enrolling company filers. We theorise the activities of the SEC and in particular its chairman at the time, Christopher Cox, over a three year period, both prior to and following the ‘credit crisis’. We argue that individuals and institutions play a central role in advancing the socio-technical project that is constituted by interactive data. We adopt insights from ANT (Callon, 1986; Latour, 1987, 2005b) and governmentality (Miller, 2008; Miller and Rose, 2008) to show how regulators and the proponents of the technology have acted as spokespersons for the interactive data technology and the retail investor. We examine the way in which calculative accountability has been privileged in the SEC’s construction of the retail investor as concerned with atomised, quantitative data (Kamuf, 2007; Roberts, 2009; Tsoukas, 1997). We find that the possibilities for the democratising effects of digital information on the Internet has not been realised in the interactive data project and that it contains risks for the very investors the SEC claims to seek to protect.

The two forms of visuo-spatial perspective taking are differently embodied and subserve different spatial prepositions

We set out to distinguish level 1 (VPT-1) and level 2 (VPT-2) perspective taking with respect to the embodied nature of the underlying processes as well as to investigate their dependence or independence of response modality (motor vs. verbal). While VPT-1 reflects understanding of what lies within someone else’s line of sight, VPT-2 involves mentally adopting someone else’s spatial point of view. Perspective taking is a high-level conscious and deliberate mental transformation that is crucially placed at the convergence of perception, mental imagery, communication, and even theory of mind in the case of VPT-2. The differences between VPT-1 and VPT-2 mark a qualitative boundary between humans and apes, with the latter being capable of VPT-1 but not of VPT-2. However, our recent data showed that VPT-2 is best conceptualized as the deliberate simulation or emulation of a movement, thus underpinning its embodied origins. In the work presented here we compared VPT-2 to VPT-1 and found that VPT-1 is not at all, or very differently embodied. In a second experiment we replicated the qualitatively different patterns for VPT-1 and VPT-2 with verbal responses that employed spatial prepositions. We conclude that VPT-1 is the cognitive process that subserves verbal localizations using “in front” and “behind,” while VPT-2 subserves “left” and “right” from a perspective other than the egocentric. We further conclude that both processes are grounded and situated, but only VPT-2 is embodied in the form of a deliberate movement simulation that increases in mental effort with distance and incongruent proprioception. The differences in cognitive effort predict differences in the use of the associated prepositions. Our findings, therefore, shed light on the situated, grounded and embodied basis of spatial localizations and on the psychology of their use.

IL-8 released constitutively by primary bronchial epithelial cells in culture forms an inactive complex with secretory component

The bronchial epithelium is a source of both α and β chemokines and, uniquely, of secretory component (SC), the extracellular ligand-binding domain of the polymeric IgA receptor. Ig superfamily relatives of SC, such as IgG and α2-macroglobulin, bind IL-8. Therefore, we tested the hypothesis that SC binds IL-8, modifying its activity as a neutrophil chemoattractant. Primary bronchial epithelial cells were cultured under conditions to optimize SC synthesis. The chemokines IL-8, epithelial neutrophil-activating peptide-78, growth-related oncogene α, and RANTES were released constitutively by epithelial cells from both normal and asthmatic donors and detected in high m.w. complexes with SC. There were no qualitative differences in the production of SC-chemokine complexes by epithelial cells from normal or asthmatic donors, and in all cases this was the only form of chemokine detected. SC contains 15% N-linked carbohydrate, and complete deglycosylation with peptide N-glycosidase F abolished IL-8 binding. In micro-Boyden chamber assays, no IL-8-dependent neutrophil chemotactic responses to epithelial culture supernatants could be demonstrated. SC dose-dependently (IC50 ∼0.3 nM) inhibited the neutrophil chemotactic response to rIL-8 (10 nM) in micro-Boyden chamber assays and also inhibited IL-8-mediated neutrophil transendothelial migration. SC inhibited the binding of IL-8 to nonspecific binding sites on polycarbonate filters and endothelial cell monolayers, and therefore the formation of haptotactic gradients, without effects on IL-8 binding to specific receptors on neutrophils. The data indicate that in the airways IL-8 may be solubilized and inactivated by binding to SC

Differential control of two forms of glutamate release by group III metabotropic glutamate receptors at rat entorhinal synapses

Neurotransmitter release at CNS synapses occurs via both action potential-dependent and independent mechanisms, and it has generally been accepted that these two forms of release are regulated in parallel. We examined the effects of activation of group III metabotropic glutamate receptors (mGluRs) on stimulus-evoked and spontaneous glutamate release onto entorhinal cortical neurones in rats, and found a differential regulation of action potential-dependent and independent forms of release. Activation of presynaptic mGluRs depressed the amplitude of stimulus-evoked excitatory postsynaptic currents, but concurrently enhanced the frequency of spontaneous excitatory currents. Moreover, these differential effects on glutamate release were mediated by pharmacologically separable mechanisms. Application of the specific activator of adenylyl cyclase, forskolin, mimicked the effect of mGluR activation on spontaneous, but not evoked release, and inhibition of adenylyl cyclase with 9-tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) blocked mGluR-mediated enhancement of spontaneous release, but not depression of evoked release. Occlusion studies with calcium channel blockers suggested that the group III mGluRs might depress evoked release through inhibition of both N and P/Q, but not R-type calcium channels. We suggest that the concurrent depression of action potential-evoked, and enhancement of action potential-independent glutamate release operate through discrete second messenger/effector systems at excitatory entorhinal terminals in rat brain. © 2007 IBRO.

Logic Based Pattern Recognition - Ontology Content (2)

Logic based Pattern Recognition extends the well known similarity models, where the distance measure is the base instrument for recognition. Initial part (1) of current publication in iTECH-06 reduces the logic based recognition models to the reduced disjunctive normal forms of partially defined Boolean functions. This step appears as a way to alternative pattern recognition instruments through combining metric and logic hypotheses and features, leading to studies of logic forms, hypotheses, hierarchies of hypotheses and effective algorithmic solutions. Current part (2) provides probabilistic conclusions on effective recognition by logic means in a model environment of binary attributes.

Solid oral forms availability in children:a cost saving investigation

AIM: To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. METHOD: Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. RESULTS: Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of 5K and 8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of 238K and 410K (single institution). CONCLUSION: Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules.